Endogenous Opioids and Opioid Receptors

endogenous opioidsThe term opioids are not new to many, it has been heard as the media is always abreast with all information about these opioid drugs which to the public are known mostly for the wrong reasons. People have got misinformed about these drugs so much that when you tell a layman that these drugs are used in hospital then to him you will something much worse than an alien. However to the medical fraternity these opioids are essentials that are hard to survive without. That said and left, back to the topic; Endogenous Opioids is a new term to many and if your prediction is as right as mine then you are hearing it for the first time. What does it really mean? The endogenous opioids are opiate-like substance, such as an endorphin, produced by the body. If you thought that you can live without these endogenous opioids then you need to wake up from your momentary slumber. Every day of our lives we face pain of all sorts even the most insignificant pains needs the actions of these opioids to give you peace.

Today, the endogenous opioid system is one of the most studied innate pain-relieving systems. The endogenous opioid system consists of widely scattered neurons that produce three opioids: beta-endorphin, the met- and leu-enkephalins, and the dynorphins. These opioids act as neurotransmitters and neuromodulators at three major classes of receptors, termed mu, delta, and kappa, and produce analgesia. The endogenous opioids works in the same manner as the narcotic opioids in that they bind to the same receptors and they also have both good and negative effects. There might be all sorts of information out there that you can lay your hands that may speak well of the opioids but the bitter truth is we all depend on despite the negative light they have been portrayed in.We are all naturally dependent on opioids for our emotional health. Both narcotics and internally generated endogenous opioids exert their action on the body by interacting with specific membrane receptor-proteins on our nerve cells.

There are three large pro-compounds that are produced by the body and these are: proenkephalin, prodynorphin, and pro-opiomelanocortin. However, endorphins can further decompose to small fragments, oligomers, which are still active. Oligomers pass the blood-brain barrier more readily. Enzymatic degradation of small-chain endorphins is accomplished by dipeptidyl carboxypeptidase, enkephalinases, angiotensinases, and other enzymes. This limits their lifetime in the unbound state.

Presynaptically opioid receptors inhibit transmission of excitatory pathways. These pathways include acetylcholine, the catecholamines, serotonin, and substance P. Substance P is a neuropeptide active in neurons that mediate our sense of pain. Endogenous opioids are also involved in glucose regulation. Opioid receptors are functionally designated as mu, delta, kappa among others. These categories can be further sub-classified by function or structure. Decoding the human genome has allowed the genetic switching-mechanisms that control the expression of each opioid receptor to be determined at the transcriptional and post-transcriptional level.

Opioid-driven inhibition of neuronal excitability is mediated by the activation of a variety of potassium channels in the plasma membrane. The disparate subjective and behavioral effects evoked by activation of the different categories of opioid receptor are typically not the outcome of different cellular responses, but reflect the different anatomical distributions of each receptor. Unlike kappa opioid receptors, however, both mu and delta opioid receptors internalize on exposure to agonists. Activation of any type of opioid receptor inhibits adenylate cyclase, resulting in a fall in intracellular cAMP and diminished action potential firing. This causes a reduced flow of nociceptive information to the brain. Conversely, opioid addicts undergoing withdrawal suffer elevated cAMP levels and enhanced protein kinase A activity, resulting in increased neurotransmitter release.

Role of Mu receptors in addiction

The Mu opioid receptors are the gateway to addiction. This is because they mediate positive reinforcement following direct or indirect activation. In an experiment where mice without mu receptors were used, it was found that the morphine’s analgesic and addictive properties are abolished in these mice. This shows that mu receptors mediate both the therapeutic and the adverse activities of opioids. The mice that were lacking mu receptors were found to lack of morphine-induced analgesia, reward, and dependence. The mice had increased sensitivity to pain. This shows that the mu receptors play a critical role in addiction. These mu receptors function as switches upon direct or indirect reinforcement of opioid abuse. Mu-opioid receptors are a key molecular switch triggering brain reward systems and potentially initiating addictive behaviors. The lack of mu-receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence. This receptor therefore mediates therapeutic analgesia and adverse activities of morphine.

Opioid withdrawal symptom

endogenous opioidsWhen a person has been using the opioids for some time, he will become physically adapted to the drugs so much that when he stops abruptly he will experience the symptoms of withdrawal. Withdrawal is not only faced by opioid user only but also other sick people who are on other drugs as well. However to limit the withdrawal symptoms, there are some factors that come in handy. One of these factors is the pace and how you exit from using these drugs. Your doctor will be of help in helping you by developing safe exit strategies that will limit the withdrawal symptoms.

Finally, you need more information to stay away from dependence on alcohol and drugs as these have crippled societies and that is why here at AWAREmed we are dedicated to finding the best solutions to addiction and dependence on substances. Dr. Dalal Akoury (MD) is always in the mood of helping any patient to be addiction free. Do not hesitate to call on her for help in managing any sort of chronic pain or any type of addiction as well as other diseases.

Endogenous Opioids and Opioid Receptors